This invention relates to 1-carba(1-dethia)-cephem antibiotics, to pharmaceutical formulations comprising the antibiotics, and to a method for the treatment of infectious diseases in man and other animals.
The 1-carba(1-dethia)cephem antibiotics have the bicyclic ring system represented by the following formula wherein the numbering system is that commonly employed in the arbitrary cepham nomenclature system. ##STR3##
The 1-carba(1-dethia)cephems are referred to herein for convenience as 1-carba-3-cephem-4-carboxylic acids or numbered derivatives thereof.
The preparation of 1-carbacephalosporins (or 1-carba(dethia)-3-cephems) and C-3 substituted methyl derivatives thereof is taught broadly by Christensen et al., in U.S. Pat. No. 4,222,866. Hirata et al., in U.K. patent application No. 2041923, teach a method for preparing 3-H and 3-halo 1-carbacephalosporins, while Hatanaka et al., Tetrahedron Letters, 24, No. 44, pp. 4837-4838 (1983) teach a method for preparing a 3-hydroxy-(.+-.)-1-carbacephalosporin.
In the field of antibacterial therapy, the need for new chemotherapeutic agents is one that will never extinguish. Mutant strains resistant to existing antibacterial agents are encountered frequently. In particular, many strains of Staph. aureus and Staph. epi (so-called methicillin resistant Staph. (MRS)) are becoming increasingly resistant to available antibacterial agents. (see, for example, Phillips, I., and Cookson, B., J. Appl. Bacteriology 67(6), 1989). To meet this need, considerable research effort continues to focus on such new agents. The present invention provides antibacterial agents useful against a wide variety of gram-positive and gram-negative bacteria. The compounds of the present invention are especially useful against these methicillin-resistant Staph. organisms.